Nickel-Catalyzed Kumada Cross-Coupling Reactions of Benzylic Sulfonamides.

Herein, we report a Kumada cross-coupling reaction of benzylic sulfonamides. The scope of the transformation includes acyclic and cyclic sulfonamide precursors that cleanly produce highly substituted acyclic fragments. Preliminary data are consistent with a stereospecific mechanism that allows for a diastereoselective reaction.

Engaging Sulfonamides: Intramolecular Cross-Electrophile Coupling Reaction of Sulfonamides with Alkyl Chlorides.

The application of amine derivatives as coupling partners is rare due to the inherent strength of the C-N bond. Herein, we report the first cross-electrophile coupling reaction of unstrained benzylic sulfonamides. Nickel-catalyzed intramolecular cross-electrophile coupling reactions of acyclic and cyclic benzylic sulfonamides with pendant alkyl chlorides generate cyclopropane products. Mechanistic experiments and DFT calculations are consistent with initiation of the reaction by magnesium iodide accelerated oxidative addition of the benzylic sulfonamide. This work establishes neutral and unstrained amine derivatives as XEC partners, furnishes structural rearrangement of benzylic sulfonamides, and provides valuable information regarding catalyst design for the development of new cross-electrophile coupling reactions of carbon-heteroatom bonds.

Enantioselective Vanadium-Catalyzed Oxidative Coupling: Development and Mechanistic Insights.

The evolution of a more reactive chiral vanadium catalyst for enantioselective oxidative coupling of phenols is reported, ultimately resulting in a simple monomeric vanadium species combined with a Brønsted or Lewis acid additive. The resultant vanadium complex is found to effect the asymmetric oxidative ortho-ortho coupling of simple phenols and 2-hydroxycarbazoles with good to excellent levels of enantioselectivity. Experimental and quantum mechanical studies of the mechanism indicate that the additives aggregate the vanadium monomers. In addition, a singlet to triplet crossover is implicated prior to carbon-carbon bond formation. The two lowest energy diastereomeric transition states leading to the enantiomeric products differ substantially with the path to the minor enantiomer involving greater torsional strain between the two phenol moieties.

Synthesis of Vicinal Carbocycles by Intramolecular Nickel-Catalyzed Conjunctive Cross-Electrophile Coupling Reaction.

A nickel-catalyzed intramolecular conjunctive cross-electrophile coupling reaction has been established. This method enables the synthesis of 3,5-vicinal carbocyclic rings found in numerous biologically active compounds and natural products. We provide mechanistic experiments that indicate this reaction proceeds through alkyl iodides formed in situ, initiates at the secondary electrophilic center, and proceeds through radical intermediates.

Asymmetric Oxidative Coupling of Phenols and Hydroxycarbazoles.

The first examples of asymmetric oxidative coupling of simple phenols and 2-hydroxycarbazoles are outlined. Generation of a more vanadium catalyst by ligand design and by addition of an exogenous Brønsted or Lewis acid was found to be key to coupling the more oxidatively resistant phenols. The resultant vanadium complex is both more Lewis acidic and more strongly oxidizing. Good to excellent levels of enantioselectivity could be obtained, and simple trituration readily provided the products with ≥95% ee.

Hepatitis E in England and Wales.

In 2005, 329 cases of hepatitis E virus infection were confirmed in England and Wales; 33 were confirmed indigenous infections, and a further 67 were estimated to be indigenous infections. Hepatitis E should be considered in the investigation of patients with hepatitis even if they have no history of travel.

The effect of malaria on mortality in a cohort of HIV-infected Ugandan adults.

OBJECTIVES: To investigate the effects of malaria parasitaemia and clinical malaria on mortality in HIV seropositive and seronegative adults. METHODS: A cohort of adults in rural Uganda were followed from 1990 to 1998. Participants attended routine clinic visits every 3 months and also when sick (interim visits). Information was collected on HIV serostatus, history of fever, current fever and malaria parasite levels. Malaria was categorized as any parasitaemia, significant parasitaemia (>/=1.25 x 10(6) parasites/ml at routine or >/=50 parasites per 200 white blood cells at interim visits) or clinical malaria. The effect of malaria on all-cause mortality was assessed using Cox models. RESULTS: The 222 HIV seropositive participants made 2762 routine visits and 1522 interim visits. During follow-up, of the 211 participants with full records, 69% had at least one episode of parasitaemia, 51% experienced significant parasitaemia and 28% had clinical malaria. There were 90 deaths in 922 person-years of observation. There were no significant associations between numbers of visits with any parasitaemia, significant parasitaemia or clinical malaria on mortality rates. The highest mortality rates were observed in those making four or more routine visits with significant parasitaemia [adjusted mortality rate ratio (RR) 3.27 compared with those making 0 such visits; P=0.078] and those making two or more visits with clinical malaria (adjusted RR 2.23; P=0.093). There was no significant interaction between any malaria category and HIV serostatus. Conclusion We found no evidence of a strong detrimental effect of malaria on all-cause mortality in HIV seropositive adults in this setting.